Junctional adhesion molecule C (JAM-C) is a transmembrane
protein with significant roles in regulation of endothelial cell (EC) functions, including immune cell recruitment and angiogenesis. As these responses are important in promoting
tumor growth, the role of EC JAM-C in
tumor development was investigated using the ID8 syngeneic model of
ovarian cancer. Within 10-15 wk, intraperitoneally injected ID8 cells form multiple
tumor deposits and
ascites that resemble human high-grade serous
ovarian cancer. Compared to wild-type mice, survival in this model was increased in EC JAM-C knockouts (KOs; 88 vs. 96 d, P=0.04) and reduced in EC JAM-C transgenics (88 vs. 78.5 d, P=0.03), mice deficient in or overexpressing EC JAM-C, respectively. While
tumor growth was significantly reduced in EC JAM-C KOs (87% inhibition
at 10 wk, P<0.0005), this was not associated with alterations in
tumor vessel density or immune cell infiltration. However,
tumor microvessels from EC JAM-C-deficient mice exhibited reduced pericyte coverage and increased vascular leakage, suggesting a role for EC JAM-C in the development of functional
tumor vessels. These findings provide evidence for a role for EC JAM-C in
tumor growth and aggressiveness as well as recruitment of pericytes to newly formed blood vessels in a model of
ovarian cancer.